Colloidal volume expanders are used to maintain normal plasma volume and blood pressure in patients. Each of these expanders, e.g. dextran, has a distribution of molecular weights (MW's). Mn determines oncotic pressure. Until now, Mw has been easier to determine than Mn, and, thus, has been used primarily. A new SEC-HPLC method permits facile measurement of both MW's. Some clinicians erroneously attribute the expansion properties of dextran to "water binding capacity" and claim that oncotic pressure is independent of Mn. To clarify the issue, we have used osmotic pressure data from CBER and the literature to show that the oncotic effect of dextran is correctly predicted by Mn. The dextrans for which osmotic pressures were considered range in Mn from 24,000 to 375,000. 3 osmotic or virial coefficients (Mn, B2, and B3) provide a sufficient mathematical representation of the osmotic properties of each of these dextrans alone. We have found that B2 is a function of Mn, in accord with theory, whereas B3 is independent of Mn thereby yielding universal values for B2 and B3. These universal virial coefficients successfully reproduce experimental osmotic pressures for all these dextrans over a concentration range of 5-60 mg/mL with a small RMS deviation. These Mn values, concentrations, and pressures include those dextrans (and concentrations) for which a water binding mechanism has been ascribed. Such a mechanism is clearly not only superfluous but incorrect. Furthermore, with limited data for the Dextran 70 and 40 products, we have been able to reproduce the experimental MW distribution, i.e. the SEC-HPLC elution profile determined during MW determinations, from Mw and Mn values only thereby providing a further rationale for using both Mw and Mn to characterize these products. Additionally, with reliable clinical data indicating average volumes of each product per kg of body mass required for fluid resuscitation, the universal virial coefficients may permit a determination of the nominal MW cut-off of the vascular bed for the dextrans. Such cut-off information would be useful in estimating the effective in vivo Mn values and, therefore, the oncotic pressure that develops as the result of the infusion of the drug product. In addition, we are, currently, endeavoring to improve a non-linear least squares fitting program that is a critical part of the SEC-HPLC methodology that is to be used to determine Mw and Mn.